In vivo spectrophotometric determination of striatal acetylcholinesterase activity: the modulation induced by the antidepressant amitriptyline.
A new technology called in vivo spectrophotometry was applied to the quantitative determination of the variations in local acetylcholinesterase (AChE) activities. Repeated measurements of the enzyme activities in the same live animal allowed the study of the in vivo inhibition of AChE by amitriptyline. Interactions between AChE and this tricyclic antidepressant were investigated at the striatal level in anesthetized rats. In this anesthetized model, AChE assays were shown to be stable for approximately 8 h. The dose-effect relationship was explored in the 2.5- to 50-mg/kg amitriptyline range. A reversible inhibition was observed after acute amitriptyline administration. The maximum of inhibition appeared between 90 and 210 min after the intoxication and reached up to 22% for the 50-mg/kg dose. The threshold dose was established as 8 mg/kg. Evidence for an indirect interaction between tricyclic antidepressant and AChE was demonstrated when the total integrity of the biological system was preserved.
Chappey
O
O
INSERM U 26, Hospital F. Widal, Paris, France.
Testylier
G
G
Gourmelon
P
P
Galonnier
M
M
Bourre
J M
JM
Fatome
M
M
Scherrmann
J M
JM
Viret
J
J
D000110:Acetylcholinesterase / Q000378:metabolism*; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D004228:Dithionitrobenzoic Acid; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry / Q000295:instrumentation / Q000379:methods; D013997:Time Factors
D000639:Amitriptyline; D004228:Dithionitrobenzoic Acid; D000110:Acetylcholinesterase